The humoral determinants of rnin release in man and the mechanisms of angiotensin II formation in the intact dog will be examined. Angiotensin II, norepinephrine, epinephrine, aldosterone, acetylcholine and solutions containing varying concentrations of potassium and sodium will be infused directly into the renal artery of normotensive and later hypertensive man. The action of these agents in the presence of superimposed alpha or beta blockade or of atropine will be examined, levels of the agents infused will be kept as close to the physiologic range as monitoring techniques permit. Renin activity, angiotensin II content, and wherever appropriate, Na plus and N plus, in systemic artery and renal vein will be measured. Renal blood flow will be determined and renin and angiotensin II release calculated from renal blood flow, hematocrit, and arterial and renal venous renin concentrations. In this way, information about the direct influence of a number or hormones and electrolytes on human renal renin and angiotensin II production independent of total body electrolyte balance and systemic hemodynamic changes will be obtained. Differing responses in normal and hypertensive kidneys may have pathophysiologic significance. Angiotensin II production will be further examined by study of the mechanism of pulmonary conversion of angiotensin I to II in the intact dog and in plasma. Angiotensin I and its various D-amino acid analogs will be synthesized and tested for intrinsic biological activity and suitability as substrate for pulmonary and plasma converting enzymes. Peptides will be injected into the pulmonary circulation of dogs, and the pulmonary venous effluent analyzed for angiotensin I, angiotensin II, and metabolites by chromatoelctrophoresis and gamma counting. Peptides which block the conversion of angiotensin I to II will be evaluated in this system. Such compounds could have therapeutic implications for certain kinds ofhuman hypertension. Disorders of humanplasma converting enzyme activity will be sought in patients with pulmonary disease and hypertension of various etiologies.